Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant inherited cancer syndrome that affects tissues derived from neural ectoderm. Since early diagnosis and treatment of MEN 2 patients significantly reduces morbidity and mortality, pre-clinical screening is the most important tool for clinical management of MEN2 families. The MEN2 gene has recently been identified as the RET Proto-oncogene. This has allowed the development of direct mutation analysis to identify the gene carriers in MEN2 families with 100% certainty using a simple DNA test. In this study, we will screen for germline RET mutations at codons 609, 611, 618, 620, 634, 918, and at any newly identified codons from a known affected individual in each MEN2 family. Subsequently, we will then screen for the identified RET mutation from asymptotic relatives of this affected individual. Furthermore , we will screen for possible RET mutations in both leukocytes and tumors from patients with apparently sporadic medullary thyroid carcinoma, especially from patients with bilateral medullary thyroid carcinoma. Finally, we will correlate the presence and nature of RET mutation with patients' clinical outcomes.